1. Field of the Invention
The present invention is related generally to the field of microscopy, and more particularly to the configuration of optical microscopes and microscope-based electronic imaging systems.
2. Description of the Related Art
In its most basic form, a microscope typically includes a base, a plate or stage for holding a sample, a magnifier commonly including a series of lenses, and a viewer for presenting a magnified image to an observer. The principal purpose of a microscope is to create a magnified image of a sample of a specimen and to accurately present the enlarged image to an observer or to an electronic imaging apparatus used for image acquisition, display, measurement, analysis, communication, archiving, or data management.
Over the years, microscopes have evolved into very complex and sophisticated optical instruments, taking a variety of forms. While most microscopes are manually operable and may present a magnified image for viewing by an operator, one of the most important recent advances in microscopy has been the development of automated, computer-aided microscopes. Most computer-aided microscopes include the conventional elements of manually operated microscopes but are further configured in combination with a digital computer. The computer may serve a variety of functions, such as, for instance, controlling the position of a motorized stage, controlling the focusing system, or controlling other optical components such as microscope objectives.
In a typical arrangement, a computer-aided microscope system includes an electronic photodetector or imaging system such as a video or CCD camera interconnected to the viewer, with the output from the detector being fed into a computer processor for a variety of finctions including analysis or image enhancement or display. The computer processor in turn may provide control signals to the microscope, for instance, to control the stage position, focus drive or other aspects of the system. Provided with this arrangement, a computer-aided microscope may enable the automatic analysis of a wide variety of objects, such as cytological samples, pathology specimens or semiconductor chips (solid state devices). Further, the automated analysis may be easily enhanced by appropriate computer programming as well as by the addition of assorted peripherals (such as data storage devices and interactive user-input devices).
In automated cytology sample analyses, for instance, a specimen is drawn from a patient, a sample is prepared from that specimen, and the sample is placed into the automated microscope. An image detector (e.g., CCD camera) may electronically scan the sample and thereby receive digital images of discrete regions of the sample. The detector may then feed these digital images to a processor, which stores the images in memory and analyzes the images. In addition, the processor may receive from the microscope an indication of the spatial coordinates of the stage (e.g., X and Y planar coordinates, and a Z focus coordinate). Through complex image analysis algorithms, the processor may identify cellular matter of interest in the sample and may then mark in memory an indication of the stage position coordinates associated with that cellular matter. Samples may be deposited on slides with fiducial marks to ensure that the X-Y locations are accurate from microscope to microscope or calibration procedures can be developed and used to ensure that the X-Y coordinates apply from machine to machine.
In turn, once the processor completes its analysis, it may generate a routing function keyed to the stage coordinates and defining an order by which the automated microscope should present areas of the sample to an operator such as a cytotechnologist. Through use of this routing function, the computer processor may thus control the microscope stage position and microscope focus, and may thereby present the cellular matter or other objects or optical fields of interest to the operator through the microscope field of view. In addition, or alternatively, the automated-microscope system may be configured to include a computer monitor, which may present the microscopic fields of view to the operator without requiring the operator to look through the microscope ocular(s).
As a general rule, precision, accuracy and speed are critical to the useful operation of a microscope in addition to the quality (e.g., resolution) of the optical magnification devices and processes. This is particularly important for computer-aided microscopy systems. In cytological specimen analysis, for instance, a cytotechnologist typically needs to be able to locate atypical or abnormal cells in specimens rapidly, precisely and accurately, since cells are typically less than a few hundred microns in their maximum linear dimension. While many cancer-related cytological changes are characteristic and can be detected and classified with a high degree of accuracy by an appropriately configured microscope, inaccurate or imprecise microscope configurations can be the source of unacceptable false positive or false negative cell classifications and sample specimen diagnoses.
Further, modem vision systems employing computer-aided image analysis have imposed on microscopes even more stringent requirements for high precision, mechanical stability and optical and illumination repeatability. Unfortunately, however, traditional mechanical (e.g., fully manual) microscope systems, as well as many of the currently available automated microscope systems, have not provided the positional accuracy, repeatability, stability and resolution required for reliable, reproducible quantitative microscopic imaging applications.
To ensure proper operation, for instance, a microscope must be as stable as possible. The microscope must be stable in the presence of ambient vibrations and also stable with respect to internally introduced vibrations. However, the motorized stages in some existing automated-microscope configurations are unstable. Consequently, these existing systems cannot rapidly, accurately, precisely and repeatedly locate and focus on diagnostically significant areas of a sample from a specimen.
Traditional optical microscopes, for example, enable movement of the stage by way of a cantilevered system that is offset from the optical path of the microscope. In other systems, as the present inventors have recognized, the stage is moved through the exertion of a force at a position other than the center of gravity or center of effort of the plate. Consequently, existing microscopes tend to generate yaw, pitch, roll and droop errors (i.e., introduce a third derivative, "jerk") during stage movement. These errors are particularly troublesome in the context of automated computer-aided microscopy. It is also problematic for human observers who also need stage motion to be dampened before they can visualize a temporally stable image.
Similarly, in microscope systems that employs a detector (such as a camera) to capture magnified images, the detector itself must remain stable during operation. However, in most such systems, the detector is attached only to the viewer of the microscope. As recognized by the present inventors, this configuration thereby increases the likelihood that the camera will become unstable or misaligned during operation, potentially rendering the camera unable to capture magnified images properly.
Further, to ensure proper operation, the sample being analyzed in a microscope needs to be properly illuminated and have proper spectral density. This is particularly the case in microscopes that employ detectors, such as cameras, to capture magnified images, as the detectors are often configured to operate optimally with a particular level of light. This is also the case whenever there is spectral-based analysis of a sample. In these systems, if the sample is illuminated with insufficient or excessive light, or with improper spectral characteristics, the detector may need to compensate for the imperfect illumination and thereby operate less than optimally. Still further, the level of illumination in a microscope is important even for manual viewing through the oculars, as appropriate illumination is required to allow human perception of the magnified sample through the microscope lenses.
Additionally, a typical microscope includes a variety of adjustable elements. These elements include, for instance, condenser lens focus, condenser lens centration, lamp filament centration, condenser aperture, and field diaphragm. To ensure proper operation of the microscope system, most or all of these elements need to be adjusted by an operator or an automated controller before analysis can begin. For example, to properly focus a diffused image at the light source, the condenser lens focus must be properly adjusted. As another example, to achieve lamp photon emitter centration, an operator must typically adjust the microscope light source if the light source is not properly centered. Unfortunately, however, adjustment of these elements can be time consuming and tedious.
In view of the deficiencies in the art, there is a need for an improved configuration of a high-precision, automated or computer-aided microscope.